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Wood C, Moheet A, Vigers T, Granados A, Lorenz A, Hanley E, Zemanick E, Chan CL. Hemoglobin A1c in youth and adults with cystic fibrosis related diabetes decreases after elexacaftor-tezacaftor-ivacaftor. J Cyst Fibros 2025:S1569-1993(25)00075-X. [PMID: 40089409 DOI: 10.1016/j.jcf.2025.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 02/26/2025] [Accepted: 03/06/2025] [Indexed: 03/17/2025]
Abstract
BACKGROUND Elexacaftor/tezacaftor/ivacaftor (ETI) has been highly effective for improving pulmonary disease and nutritional outcomes. However, the effect of this therapy on glycemic control in people with cystic fibrosis related diabetes (CFRD) is unclear. This study aimed to examine real-world effects of ETI on glycemia as captured by hemoglobin A1c (HbA1c) in people with pre-existing CFRD. METHODS Retrospective chart review was performed at 4 US CF centers. Individuals with CFRD included in the study started ETI before December 2020, and had an HbA1c within 1 year before and up to 2 years after ETI initiation. A sub-analysis comparing CGM data and insulin dosing within the year before and after ETI was performed. Summary statistics were calculated and within-subject results compared. RESULTS A total 175 individuals with CFRD had HbA1c data before and after ETI. Mean (±SD) age was 32.4 (±12.4) years, 49.1 % female. HbA1c were compared a median (IQR) of -40 (-93, 0) days before and 290 (107, 441) days after ETI initiation. Median (IQR) HbA1c decreased from 6.4 % (5.8, 7.2) to 6.0 % (5.5, 6.8), p<0.001. A subgroup of 13 individuals had CGM and basal insulin data for comparison. No changes were observed in CGM metrics, however, basal insulin dose in these patients decreased (p=0.03). CONCLUSION Findings suggest clinical improvements in glycemia following ETI initiation in people with CFRD. Further studies are required to better understand the mechanisms by which ETI may modulate insulin and glucose dynamics in individuals with existing CFRD.
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Affiliation(s)
| | - Amir Moheet
- Department of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Tim Vigers
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA; Department of Biostatistics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Andrea Granados
- Department of Pediatrics, Nicklaus Children's Hospital, Miami, FL, USA
| | - Andrea Lorenz
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA
| | - Elinor Hanley
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA
| | - Edith Zemanick
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA
| | - Christine L Chan
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA
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Tönnies T, Voeltz D, Voß S, Hoyer A, Brinks R. Future prevalence of type 2 diabetes in Germany: a projection until 2040 including incidence trends observed during the SARS-CoV-2 pandemic. FRONTIERS IN EPIDEMIOLOGY 2025; 5:1388189. [PMID: 40040960 PMCID: PMC11876116 DOI: 10.3389/fepid.2025.1388189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Accepted: 02/06/2025] [Indexed: 03/06/2025]
Abstract
Introduction Previous studies indicate that the prevalence of type 2 diabetes (T2D) will increase substantially over the coming decades. One projection from 2019 estimated an increase in prevalence in Germany by 54% to 77% (depending on future trends in incidence and mortality) between 2015 and 2040. We aim to update this projection by incorporating recently published trends in T2D incidence in Germany that include the changes during the SARS-CoV-2 pandemic. Materials and methods We used a partial differential equation that describes the illness-death model to project the age- and sex-specific T2D prevalence among adults between 2015 and 2040. This required input data for the age- and sex-specific incidence, mortality of the general population, mortality rate ratio of people with vs. without T2D and prevalence in the initial year of the projection. We considered five scenarios with different future trends in incidence and their impact on prevalence. Using the most recently available data on T2D incidence, we assumed that the incidence remains constant as observed in 2021 for the whole projection horizon (first scenario). In further scenarios, we assumed that the observed age- and sex-specific trends in incidence between 2015 and 2021 would continue until 2025 (second scenario), 2030 (third scenario), 2035 (fourth scenario) and 2040 (fifth scenario). One additional scenario assumed that the age-specific prevalence remains constant. Results Observed trends in incidence suggest a decrease between 2015 and 2017, and a slight upward trend thereafter until 2021 in most age groups. Depending on how long these observed increases in incidence continue, the number of people with T2D in Germany will increase from 6.8 million in 2015 to between 10.9 million and 14.2 million in 2040. These numbers correspond to increases in prevalence from 10.5% in 2015 to between 15.5% and 20.1% in 2040. In the constant prevalence scenario, the overall prevalence and number of people with T2D in 2040 was 11.4% and 8.1 million, respectively. Conclusions The future prevalence of T2D in Germany strongly depends on how long the recently observed increasing trend in T2D incidence will continue, which warrants close monitoring of these trends in post-pandemic years.
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Affiliation(s)
- T. Tönnies
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at the Heinrich Heine University, Düsseldorf, Germany
- Chair for Medical Biometry and Epidemiology, Faculty of Health/School of Medicine, Witten/Herdecke University, Witten, Germany
| | - D. Voeltz
- Biostatistics and Medical Biometry, Medical School OWL, Bielefeld University, Bielefeld, Germany
- Department of Statistics, Ludwig-Maximilians-University Munich, Munich, Germany
| | - S. Voß
- Chair for Medical Biometry and Epidemiology, Faculty of Health/School of Medicine, Witten/Herdecke University, Witten, Germany
| | - A. Hoyer
- Biostatistics and Medical Biometry, Medical School OWL, Bielefeld University, Bielefeld, Germany
| | - R. Brinks
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at the Heinrich Heine University, Düsseldorf, Germany
- Chair for Medical Biometry and Epidemiology, Faculty of Health/School of Medicine, Witten/Herdecke University, Witten, Germany
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Tang SS, Zhao XF, An XD, Sun WJ, Kang XM, Sun YT, Jiang LL, Gao Q, Li ZH, Ji HY, Lian FM. Classification and identification of risk factors for type 2 diabetes. World J Diabetes 2025; 16:100371. [PMID: 39959280 PMCID: PMC11718467 DOI: 10.4239/wjd.v16.i2.100371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Revised: 10/24/2024] [Accepted: 11/26/2024] [Indexed: 12/30/2024] Open
Abstract
The risk factors for type 2 diabetes mellitus (T2DM) have been increasingly researched, but the lack of systematic identification and categorization makes it difficult for clinicians to quickly and accurately access and understand all the risk factors, which are categorized in this paper into five categories: Social determinants, lifestyle, checkable/testable risk factors, history of illness and medication, and other factors, which are discussed in a narrative review. Meanwhile, this paper points out the problems of the current research, helps to improve the systematic categorisation and practicality of T2DM risk factors, and provides a professional research basis for clinical practice and industry decision-making.
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Affiliation(s)
- Shan-Shan Tang
- College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, Jilin Province, China
| | - Xue-Fei Zhao
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Xue-Dong An
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Wen-Jie Sun
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Xiao-Min Kang
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Yu-Ting Sun
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Lin-Lin Jiang
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Qing Gao
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Ze-Hua Li
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Hang-Yu Ji
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Feng-Mei Lian
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
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Keels JN, McDonald IR, Lee CS, Dwyer AA. Antidiabetic agent use and clinical outcomes in patients with diabetes hospitalized for COVID-19: a systematic review and meta-analysis. Front Endocrinol (Lausanne) 2025; 15:1482853. [PMID: 39835258 PMCID: PMC11743176 DOI: 10.3389/fendo.2024.1482853] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Accepted: 12/09/2024] [Indexed: 01/22/2025] Open
Abstract
Background The effect of antidiabetic agents on mortality outcomes is unclear for individuals with diabetes mellitus (DM) who are hospitalized for COVID-19. Purpose To examine the relationship between antidiabetic agent use and clinical outcomes in individuals with DM hospitalized for COVID-19. Methods A systematic review of the literature (2020-2024) was performed across five databases. Included articles reported primary research (English) reporting clinical outcomes of adult patients (≥18 yrs.) with DM receiving antidiabetic agents who were hospitalized for COVID-19. Following PRISMA guidelines articles underwent independent dual review. Quality appraisal was completed for included studies. Independent reviewers used a structured data extraction form to retrieve relevant data. Aggregated data were synthesized by treatment regimen and reported descriptively. Random effects meta-analyses were performed to assess relative risk and prevalence of mortality. Results After removing duplicates, title and abstract screening of 4,898 articles identified 118 articles for full-text review and 35 articles were retained for analysis. Included articles were primarily from China (15/35, 43%) and retrospective in nature (31/35, 89%). Fourteen studies (40%) assessed multiple antidiabetic agents, fifteen studies (42%) focused on metformin, three studies (9%) assessed the use of DPP-4 inhibitors, and three single studies (9%) investigated the use of insulin, TZD, and SGLT2 inhibitors. Despite differences among studies, the overall relative risk of mortality among metformin and DPP-4 inhibitor users was 0.432 (95% CI = 0.268-0.695, z = 3.45, p < 0.001) and the overall prevalence of mortality among all antidiabetic users was 16% (95% CI = 13%-19%, z = 10.70, p < 0.001). Conclusions and implications Synthesis of findings suggest that patients who remained on oral agents (with/without supplemental insulin therapy) exhibited decreased mortality and lower inflammatory markers. Results indicate that individuals with DM should continue oral antidiabetic agents with additional basal insulin as needed to improve glycemic control and reduce mortality. Further work is needed to uncover mechanism(s) and clarify medical management approaches.
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Affiliation(s)
- Jordan N. Keels
- Boston College, William F. Connell School of Nursing, Boston, MA, United States
| | | | - Christopher S. Lee
- Boston College, William F. Connell School of Nursing, Boston, MA, United States
| | - Andrew A. Dwyer
- Boston College, William F. Connell School of Nursing, Boston, MA, United States
- P50 Massachusetts General Hospital, Harvard Center for Reproductive Medicine, Boston, MA, United States
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Matviichuk A, Yerokhovych V, Zemskov S, Ilkiv Y, Gurianov V, Shaienko Z, Falalyeyeva T, Sulaieva O, Kobyliak N. Unveiling risk factors for post-COVID-19 syndrome development in people with type 2 diabetes. Front Endocrinol (Lausanne) 2024; 15:1459171. [PMID: 39722811 PMCID: PMC11668646 DOI: 10.3389/fendo.2024.1459171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Accepted: 11/27/2024] [Indexed: 12/28/2024] Open
Abstract
Introduction Post-COVID-19 syndrome (PCS) is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-associated chronic condition characterized by long-term violations of physical and mental health. People with type 2 diabetes (T2D) are at high risk for severe COVID-19 and PCS. Aim The current study aimed to define the predictors of PCS development in people with T2D for further planning of preventive measures and improving patient outcomes. Materials and methods The data were collected through the national survey targeting persons with T2D concerning the history of COVID-19 course and signs and symptoms that developed during or after COVID-19 and continued for more than 12 weeks and were not explained by an alternative diagnosis. In total, 469 patients from different regions of Ukraine were enrolled in the study. Among them, 227 patients reported PCS development (main group), while 242 patients did not claim PCS symptoms (comparison group). Stepwise multivariate logistic regression and probabilistic neural network (PNN) models were used to select independent risk factors. Results Based on the survey data, 8 independent factors associated with the risk of PCS development in T2D patients were selected: newly diagnosed T2D (OR 4.86; 95% CI 2.55-9.28; p<0.001), female sex (OR 1.29; 95% CI 0.86-1.94; p=0.220), COVID-19 severity (OR 1.35 95% CI 1.05-1.70; p=0.018), myocardial infarction (OR 2.42 95% CI 1.26-4.64; p=0.002) and stroke (OR 3.68 95% CI 1.70-7.96; p=0.001) in anamnesis, HbA1c above 9.2% (OR 2.17 95% CI 1.37-3.43; p=0.001), and the use of insulin analogs (OR 2.28 95% CI 1.31-3.94; p=0.003) vs human insulin (OR 0.67 95% CI 0.39-1.15; p=0.146). Although obesity aggravated COVID-19 severity, it did not impact PCS development. In ROC analysis, the 8-factor multilayer perceptron (MLP) model exhibited better performance (AUC 0.808; 95% CІ 0.770-0.843), allowing the prediction of the risk of PCS development with a sensitivity of 71.4%, specificity of 76%, PPV of 73.6% and NPV of 73.9%. Conclusions Patients who were newly diagnosed with T2D, had HbA1c above 9.2%, had previous cardiovascular or cerebrovascular events, and had severe COVID-19 associated with mechanical lung ventilation were at high risk for PCS.
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Affiliation(s)
- Anton Matviichuk
- Department of Endocrinology, Bogomolets National Medical University, Kyiv, Ukraine
| | | | - Sergii Zemskov
- Department of Endocrinology, Bogomolets National Medical University, Kyiv, Ukraine
| | - Yeva Ilkiv
- Department of Endocrinology, Bogomolets National Medical University, Kyiv, Ukraine
| | - Vitalii Gurianov
- Department of Endocrinology, Bogomolets National Medical University, Kyiv, Ukraine
| | - Zlatoslava Shaienko
- Department of Endocrinology with Pediatric Infectious Diseases, Poltava State Medical University, Poltava, Ukraine
| | - Tetyana Falalyeyeva
- Department of Fundamental Medicine, Educational-Scientific Center “Institute of Biology and Medicine” Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
- Scientific Department, Medical Laboratory CSD, Kyiv, Ukraine
| | - Oksana Sulaieva
- Scientific Department, Medical Laboratory CSD, Kyiv, Ukraine
- Department of Pathology, Kyiv Medical University, Kyiv, Ukraine
| | - Nazarii Kobyliak
- Department of Endocrinology, Bogomolets National Medical University, Kyiv, Ukraine
- Scientific Department, Medical Laboratory CSD, Kyiv, Ukraine
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Bistagnino F, Pizzi D, Mantovani F, Antonino JR, Tovani-Palone MR. Long COVID and gut candidiasis: What is the existing relationship? World J Gastroenterol 2024; 30:4104-4114. [DOI: 10.3748/wjg.v30.i37.4104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 08/30/2024] [Accepted: 09/13/2024] [Indexed: 09/26/2024] Open
Abstract
Since the beginning of the coronavirus disease (COVID) 2019 pandemic, thousands of articles on the topic have been published, and although there is a growing trend of research on another associated condition, long coronavirus disease, important points still remain to be clarified in this respect. Robust evidence has suggested a relevant link between new clinical discoveries and molecular mechanisms that could be associated with the manifestations of different signs and symptoms involving cases of long COVID. However, one of the existing gaps that requires further investigation concerns a possible relationship between gut candidiasis and long COVID. While recent studies also suggest an interplay between the occurrence of these two conditions, it is not yet fully clear how this may happen, as well as the specifics regarding the possible pathophysiological mechanisms involved. In this connection and with the advent of a potential strengthening of the body of evidence supporting the hypothesis of a link between gut candidiasis and long COVID, a better understanding of the clinical presentation, pathophysiology and clinical management of such a relationship should be essential and useful for both, additional advances towards more targeted research and appropriate case management. Knowing more about the signs, symptoms, and complications associated with cases of long COVID is essential in order to more effectively mitigate the related burden and provide a higher quality of care and life for the affected population. In light of this and the need for better outcomes, here we review and discuss the content on different aspects of long COVID, including its pathophysiology and the existing evidence of a potential relationship between such a condition and gut candidiasis, as well as suggest propositions for future related research.
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Affiliation(s)
- Filippo Bistagnino
- Department of Medical Biotechnology and Translational Medicine, International Medical School, Università degli Studi di Milano, Milan 20054, Italy
| | - Davide Pizzi
- Department of Medical Biotechnology and Translational Medicine, International Medical School, Università degli Studi di Milano, Milan 20054, Italy
| | - Filippo Mantovani
- Department of Medical Biotechnology and Translational Medicine, International Medical School, Università degli Studi di Milano, Milan 20054, Italy
| | - Jacopo Rosso Antonino
- Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan 20133, Italy
| | - Marcos Roberto Tovani-Palone
- Department of Research Analytics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai 600077, India
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Cangelosi G, Mancin S, Pantanetti P, Sguanci M, Morales Palomares S, De Luca A, Biondini F, Tartaglia F, Ferrara G, Petrelli F. Impact of the COVID-19 Pandemic on Lifestyle Behavior and Clinical Care Pathway Management in Type 2 Diabetes: A Retrospective Cross-Sectional Study. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1624. [PMID: 39459411 PMCID: PMC11509258 DOI: 10.3390/medicina60101624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Revised: 09/23/2024] [Accepted: 10/02/2024] [Indexed: 10/28/2024]
Abstract
Background and Objectives: In Italy, as in the rest of the world, government restrictions aimed at containing the spread of COVID-19 primarily imposed limitations on social relationships and personal behavior. This situation significantly affected the management of chronic illnesses, including type 2 diabetes (T2D). The objective was to evaluate the perceptions of patients with T2D regarding the quality of care received during the COVID-19 pandemic and the impact on dietary and physical activity behaviors. Materials and Methods: We conducted a retrospective cross-sectional survey. Data were collected from June to July 2023 using the convenience sampling of patients with T2D, and the Patient Assessment of Chronic Illness Care (PACIC) and Medi-Lite questionnaires were administered. Results: During the research period, out of the 130 subjects who met all enrollment criteria, 103 patients were included in this study (79.23%). The results of the administered questionnaires were heterogeneous. The average scores from the PACIC Questionnaire for each question displayed significant variability, indicating a range of experiences in the quality of care. In the Medi-Lite survey, fruit, cereals, and olive oil showed the highest adherence levels, with mean scores ranging from 2.58 (SD ± 1.18) for fruit to 1.89 (SD ± 0.34) for olive oil and 1.97 (SD ± 0.17) for cereals. Patients who reported increased food intake during the lockdown attributed it to having more time to prepare meals. Physical activity levels remained unchanged for 48 patients, decreased for 45 patients, and only 9 patients managed to exercise more during the COVID-19 restrictions. Conclusions: Healthcare systems must prioritize comprehensive care plans for T2D that address not only physical health, but also emotional and social well-being. Post-pandemic, promoting healthier lifestyles and empowering patients to manage their condition is crucial. A multidisciplinary and multidimensional approach could support the care of vulnerable individuals, such as patients with T2D, especially during crises like pandemics or other dramatic events.
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Affiliation(s)
- Giovanni Cangelosi
- Unit of Diabetology, Asur Marche—Area Vasta 4 Fermo, 63900 Fermo, FM, Italy;
| | - Stefano Mancin
- IRCCS Humanitas Research Hospital, 20089 Rozzano, ML, Italy;
| | - Paola Pantanetti
- Unit of Diabetology, Asur Marche—Area Vasta 4 Fermo, 63900 Fermo, FM, Italy;
| | - Marco Sguanci
- A.O. Polyclinic San Martino Hospital, Largo R. Benzi 10, 16132 Genova, GE, Italy;
| | - Sara Morales Palomares
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy;
| | - Alessia De Luca
- School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, MC, Italy;
| | | | - Francesco Tartaglia
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, ML, Italy;
| | - Gaetano Ferrara
- Nephrology and Dialysis Unit, Ramazzini Hospital, 41012 Carpi, MO, Italy;
| | - Fabio Petrelli
- School of Pharmacy, Polo Medicina Sperimentale e Sanità Pubblica “Stefania Scuri”, 62032 Camerino, MC, Italy;
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Wong R, Hall MA, Wiggen T, Johnson SG, Huling JD, Turner LE, Wilkins KJ, Yeh HC, Stürmer T, Bramante CT, Buse JB, Reusch J, N3C Consortium. Effect of SARS-CoV-2 Infection on Incident Diabetes by Viral Variant: Findings From the National COVID Cohort Collaborative (N3C). Diabetes Care 2024; 47:1846-1854. [PMID: 39207804 PMCID: PMC11417274 DOI: 10.2337/dc24-1003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Accepted: 07/30/2024] [Indexed: 09/04/2024]
Abstract
OBJECTIVE The coronavirus 2019 (COVID-19) pandemic has evolved over time by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, disease severity, treatment, and prevention. There is evidence of an elevated risk of incident diabetes after COVID-19; our objective was to evaluate whether this association is consistent across time and with contemporary viral variants. RESEARCH DESIGN AND METHODS We conducted a retrospective cohort study using National COVID Cohort Collaborative (N3C) data to evaluate incident diabetes risk among COVID-positive adults compared with COVID-negative patients or control patients with acute respiratory illness (ARI). Cohorts were weighted on demographics, data site, and Charlson comorbidity index score. The primary outcome was the cumulative incidence ratio (CIR) of incident diabetes for each viral variant era. RESULTS Risk of incident diabetes 1 year after COVID-19 was increased for patients with any viral variant compared with COVID-negative control patients (ancestral CIR 1.16 [95% CI 1.12-1.21]; Alpha CIR 1.14 [95% CI 1.11-1.17]; Delta CIR 1.17 [95% CI 1.13-1.21]; Omicron CIR 1.13 [95% CI 1.10-1.17]) and control patients with ARI (ancestral CIR 1.17 [95% CI 1.11-1.22]; Alpha CIR 1.14 [95% CI 1.09-1.19]; Delta CIR 1.18 [95% CI 1.11-1.26]; Omicron CIR 1.20 [95% CI 1.13-1.27]). There was latency in the timing of incident diabetes risk with the Omicron variant; in contrast with other variants, the risk presented after 180 days. CONCLUSIONS Incident diabetes risk after COVID-19 was similar across different SARS-CoV-2 variants. However, there was greater latency in diabetes onset in the Omicron variant era.
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Affiliation(s)
- Rachel Wong
- Department of Biomedical Informatics, Stony Brook University, Stony Brook, NY
- Department of Internal Medicine, Stony Brook University, Stony Brook, NY
| | - Margaret A. Hall
- Department of Hematology and Medical Oncology, Emory University, Atlanta, GA
| | - Talia Wiggen
- Clinical and Translational Science Institute, University of Minnesota, Minneapolis, MN
| | - Steven G. Johnson
- Institute for Health Informatics, University of Minnesota, Minneapolis, MN
| | - Jared D. Huling
- Division of Biostatistics and Health Data Science, School of Public Health, University of Minnesota, Minneapolis, MN
| | - Lindsey E. Turner
- Division of Biostatistics and Health Data Science, School of Public Health, University of Minnesota, Minneapolis, MN
| | - Kenneth J. Wilkins
- Office of the Director, Biostatistics Program/Office of Clinical Research Support, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
| | - Hsin-Chieh Yeh
- Department of Medicine, Johns Hopkins University, Baltimore, MD
- Department of Epidemiology, Johns Hopkins University, Baltimore, MD
| | - Til Stürmer
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Carolyn T. Bramante
- Division of General Internal Medicine, University of Minnesota Medical School, Minneapolis, MN
| | - John B. Buse
- Division of Endocrinology and Metabolism, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
- North Carolina Translational and Clinical Sciences Institute, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Jane Reusch
- Division of Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO
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Debuysschere C, Nekoua MP, Alidjinou EK, Hober D. The relationship between SARS-CoV-2 infection and type 1 diabetes mellitus. Nat Rev Endocrinol 2024; 20:588-599. [PMID: 38890459 DOI: 10.1038/s41574-024-01004-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/23/2024] [Indexed: 06/20/2024]
Abstract
Environmental factors, in particular viral infections, are thought to have an important role in the pathogenesis of type 1 diabetes mellitus (T1DM). The COVID-19 pandemic reinforced this hypothesis as many observational studies and meta-analyses reported a notable increase in the incidence of T1DM following infection with SARS-CoV-2 as well as an association between SARS-CoV-2 infection and the risk of new-onset T1DM. Experimental evidence suggests that human β-cells express SARS-CoV-2 receptors and that SARS-CoV-2 can infect and replicate in β-cells, resulting in structural or functional alterations of these cells. These alterations include reduced numbers of insulin-secreting granules, impaired pro-insulin (or insulin) secretion, and β-cell transdifferentiation or dedifferentiation. The inflammatory environment induced by local or systemic SARS-CoV-2 infection might result in a set of signals (such as pro-inflammatory cytokines) that lead to β-cell alteration or apoptosis or to a bystander activation of T cells and disruption of peripheral tolerance that triggers autoimmunity. Other mechanisms, such as viral persistence, molecular mimicry and activation of endogenous human retroviruses, are also likely to be involved in the pathogenesis of T1DM following SARS-CoV-2 infection. This Review addresses the issue of the involvement of SARS-CoV-2 infection in the development of T1DM using evidence from epidemiological, clinical and experimental studies.
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Affiliation(s)
- Cyril Debuysschere
- Université de Lille, CHU Lille, Laboratoire de virologie ULR3610, Lille, France
| | | | | | - Didier Hober
- Université de Lille, CHU Lille, Laboratoire de virologie ULR3610, Lille, France.
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10
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Zhou J, Wang Y, Xu R. Association of COVID-19 infection and the risk of new incident diabetes: a systematic review and meta-analysis. Front Endocrinol (Lausanne) 2024; 15:1429848. [PMID: 39253580 PMCID: PMC11381376 DOI: 10.3389/fendo.2024.1429848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 08/08/2024] [Indexed: 09/11/2024] Open
Abstract
Background As the world population recovers from the COVID-19 infection, a series of acute sequelae emerge including new incident diabetes. However, the association between COVID-19 infection and new incident diabetes is not fully understood. We purpose to determine the risk of new incident diabetes after COVID-19 infection. Methods PubMed, Embase, and Cochrane Library were used as databases to search for cohort studies published from database inception to February 4, 2024. Two reviewers independently conducted the study screening, data extraction, and risk of bias assessment. A random-effects model was adopted to pool the hazard ratio (HR) with corresponding 95% confidence intervals (CI). Subgroup analysis was conducted to explore the potential influencing factors. Results A total of 20 cohort studies with over 60 million individuals were included. The pooling analysis illustrates the association between COVID-19 infection and an increased risk of new incident diabetes (HR = 1.46; 95% CI: 1.38-1.55). In subgroup analysis, the risk of type 1 diabetes was HR=1.44 (95% CI: 1.13-1.82), and type 2 diabetes was HR=1.47 (95% CI: 1.36-1.59). A slightly higher risk of diabetes was found in males (HR=1.37; 95% CI: 1.30-1.45) than in females (HR=1.29; 95% CI: 1.22-1.365). The risk of incident diabetes is associated with hospitalization: non-hospitalized patients have an HR of 1.16 (95% CI: 1.07-1.26), normal hospitalized patients have an HR of 2.15 (95% CI: 1.33-3.49), and patients receiving intensive care have the highest HR of 2.88 (95% CI: 1.73-4.79). Conclusions COVID-19 infection is associated with an elevated risk of new incident diabetes. Patients ever infected with COVID-19 should be recognized as a high-risk population with diabetes. Systematic review registration https://www.crd.york.ac.uk/prospero, identifier CRD42024522050.
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Affiliation(s)
- Jingye Zhou
- International Medical College, Chongqing Medical University, Chongqing, China
- College of Life Sciences, University of Leicester, Leicester, United Kingdom
| | - Yuzhu Wang
- International Medical College, Chongqing Medical University, Chongqing, China
- College of Life Sciences, University of Leicester, Leicester, United Kingdom
| | - Ruolan Xu
- International Medical College, Chongqing Medical University, Chongqing, China
- College of Life Sciences, University of Leicester, Leicester, United Kingdom
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11
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Cangelosi G, Palomares SM, Pantanetti P, De Luca A, Biondini F, Nguyen CTT, Mancin S, Sguanci M, Petrelli F. COVID-19, Nutrients and Lifestyle Eating Behaviors: A Narrative Review. Diseases 2024; 12:193. [PMID: 39195192 DOI: 10.3390/diseases12080193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Revised: 08/13/2024] [Accepted: 08/19/2024] [Indexed: 08/29/2024] Open
Abstract
BACKGROUND COVID-19 infection, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), quickly emerged as the most significant event of the new millennium. A balanced diet seems to ensure the proper functioning of the immune system and plays a fundamental role in the prevention of viral disease, inflammation, or thrombosis. The principal aim of this secondary study was to investigate the relationship between nutrients, lifestyle eating behaviors, and SARS-CoV-2 infection. METHODS A narrative review was conducted in the PubMed-Medline database, analyzing primary studies. RESULTS Our review identified 21 relevant studies: 13 focused on vitamins, 1 on omega-3 supplementation, 1 on probiotics, and 6 on lifestyle and dietary behaviors. Vitamin supplementation has shown promise in attenuating COVID-19 symptoms and reducing mortality risk. Specifically, vitamin D has demonstrated efficacy in enhancing immune responses among patients with the disease. While preliminary evidence suggests the potential benefits of omega-3 and probiotic supplementation in improving health outcomes for COVID-19 outpatients, further research is needed to solidify these findings. CONCLUSIONS The lifestyle changes imposed by lockdown measures have adversely affected psychological well-being and exacerbated health issues associated with reduced physical activity and poor dietary habits.
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Affiliation(s)
| | - Sara Morales Palomares
- Department of Pharmacy, Health and Nutritional Sciences (DFSSN), University of Calabria, 87036 Rende, Italy
| | | | - Alessia De Luca
- School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy
| | | | - Cuc Thi Thu Nguyen
- Department of Pharmaceutical Administration and Economics, Hanoi University of Pharmacy, Hanoi 100000, Vietnam
| | | | - Marco Sguanci
- A.O. Polyclinic San Martino Hospital, Largo R. Benzi 10, 16132 Genova, Italy
| | - Fabio Petrelli
- School of Pharmacy, Polo Medicina Sperimentale e Sanità Pubblica "Stefania Scuri", Via Madonna delle Carceri 9, 62032 Camerino, Italy
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12
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Yanai H, Adachi H, Hakoshima M, Katsuyama H, Sako A. The Significance of Endothelial Dysfunction in Long COVID-19 for the Possible Future Pandemic of Chronic Kidney Disease and Cardiovascular Disease. Biomolecules 2024; 14:965. [PMID: 39199353 PMCID: PMC11352301 DOI: 10.3390/biom14080965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 07/23/2024] [Accepted: 08/06/2024] [Indexed: 09/01/2024] Open
Abstract
Various symptoms have been reported to persist beyond the acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which is referred to as long coronavirus disease 19 (long COVID-19). Over 65 million individuals suffer from long COVID-19. However, the causes of long COVID-19 are largely unknown. Since long COVID-19 symptoms are observed throughout the body, vascular endothelial dysfunction is a strong candidate explaining the induction of long COVID-19. The angiotensin-converting enzyme 2 (ACE2), the entry receptor for SARS-CoV-2, is ubiquitously expressed in endothelial cells. We previously found that the risk factors for atherosclerotic cardiovascular disease (ASCVD) and a history of ASCVD raise the risk of severe COVID-19, suggesting a contribution of pre-existing endothelial dysfunction to severe COVID-19. Here, we show a significant association of endothelial dysfunction with the development of long COVID-19 and show that biomarkers for endothelial dysfunction in patients with long COVID-19 are also crucial players in the development of ASCVD. We consider the influence of long COVID-19 on the development of chronic kidney disease (CKD) and ASCVD. Future assessments of the outcomes of long COVID-19 in patients resulting from therapeutic interventions that improve endothelial function may imply the significance of endothelial dysfunction in the development of long COVID-19.
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Affiliation(s)
- Hidekatsu Yanai
- Department of Diabetes, Endocrinology and Metabolism, National Center for Global Health and Medicine Kohnodai Hospital, 1-7-1 Kohnodai, Ichikawa 272-8516, Chiba, Japan; (H.A.); (M.H.); (H.K.)
| | - Hiroki Adachi
- Department of Diabetes, Endocrinology and Metabolism, National Center for Global Health and Medicine Kohnodai Hospital, 1-7-1 Kohnodai, Ichikawa 272-8516, Chiba, Japan; (H.A.); (M.H.); (H.K.)
| | - Mariko Hakoshima
- Department of Diabetes, Endocrinology and Metabolism, National Center for Global Health and Medicine Kohnodai Hospital, 1-7-1 Kohnodai, Ichikawa 272-8516, Chiba, Japan; (H.A.); (M.H.); (H.K.)
| | - Hisayuki Katsuyama
- Department of Diabetes, Endocrinology and Metabolism, National Center for Global Health and Medicine Kohnodai Hospital, 1-7-1 Kohnodai, Ichikawa 272-8516, Chiba, Japan; (H.A.); (M.H.); (H.K.)
| | - Akahito Sako
- Department of General Medicine, National Center for Global Health and Medicine Kohnodai Hospital, 1-7-1 Kohnodai, Ichikawa 272-8516, Chiba, Japan;
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13
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Price S, Bailey S, Hamilton W, Jones D, Mounce L, Abel G. The effects of the first UK lockdown for the COVID-19 pandemic on primary-care-recorded cancer and type-2 diabetes mellitus records: A population-based quasi-experimental time series study. Cancer Epidemiol 2024; 91:102605. [PMID: 38959588 DOI: 10.1016/j.canep.2024.102605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 06/18/2024] [Accepted: 06/21/2024] [Indexed: 07/05/2024]
Abstract
BACKGROUND COVID-19 disrupted consulting behaviour, healthcare delivery and cancer diagnostic services. This study quantifies the cancer incidence coded in UK general practice electronic health records and deviations from historical trends after the March 2020 national lockdown. For comparison, we study the coded incidence of type-2 diabetes mellitus, which is diagnosed almost entirely within primary care. METHODS Poisson interrupted time series models investigated the coded incidence of diagnoses in adults aged ≥ 18 years in the Clinical Practice Research Datalink before (01/03/2017-29/02/2020) and after (01/03/2020-28/02/2022) the first lockdown. Datasets were stratified by age, sex, and general practice per 28-day aggregation period. Models captured incidence changes associated with lockdown, both immediately and over time based on historical trends. RESULTS We studied 189,457 incident cancer and 191,915 incident diabetes records in 1480 general practices over 52,374,197 person-years at risk. During 01/03/2020-28/02/2022, there were fewer incident records of cancer (n = 22,199, 10.49 %, 10.44-10.53 %) and diabetes (n = 15,709, 7.57 %, 7.53-7.61 %) than expected. Within cancers, impacts ranged from no effect (e.g. unknown primary, pancreas, and ovary), to small effects for lung (n = 773, 3.11 %, 3.09-3.13 % fewer records) and female breast (n = 2686, 6.77 %, 6.73-6.81 %), to the greatest effect for bladder (n = 2874, 31.15 %, 31.00-31.31 %). Diabetes and cancer records recovered maximally to 86 % (95 %CI 80.3-92.7 %) and 74 % (95 %CI 70.3-78.6 %) in July 2021 and May 2021, respectively, of their expected values, declining again until the study end. CONCLUSION The "missing" cancer and diabetes diagnoses in primary care may comprise delayed or missed diagnoses, reduced incidence associated with excess deaths from COVID-19, and potentially increased non-coded recording of diagnoses. Future validation studies must quantify the concordance between primary care and National Cancer Registration Data and Hospital Episode Statistics over the pandemic era.
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Affiliation(s)
- Sarah Price
- Smeall Building, University of Exeter Medical School, University of Exeter, Heavitree Road, Exeter EX1 2LU, UK.
| | - Sarah Bailey
- Smeall Building, University of Exeter Medical School, University of Exeter, Heavitree Road, Exeter EX1 2LU, UK.
| | - Willie Hamilton
- Smeall Building, University of Exeter Medical School, University of Exeter, Heavitree Road, Exeter EX1 2LU, UK.
| | - Dan Jones
- Leeds Institute of Health Sciences, University of Leeds, Leeds, UK.
| | - Luke Mounce
- Smeall Building, University of Exeter Medical School, University of Exeter, Heavitree Road, Exeter EX1 2LU, UK.
| | - Gary Abel
- Smeall Building, University of Exeter Medical School, University of Exeter, Heavitree Road, Exeter EX1 2LU, UK.
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14
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Kartika R, Subekti I, Kurniawan F, Wafa S, Pradnjaparamita T, Tahapary DL, Wibowo H. Altered Body Composition and Cytokine Production in Patients with Elevated HOMA-IR after SARS-CoV-2 Infection: A 12-Month Longitudinal Study. Biomedicines 2024; 12:1581. [PMID: 39062154 PMCID: PMC11274364 DOI: 10.3390/biomedicines12071581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 06/24/2024] [Accepted: 06/28/2024] [Indexed: 07/28/2024] Open
Abstract
Altered body composition and cytokine production due to SARS-CoV-2 antigens may affect homeostasis model assessment for insulin resistance (HOMA-IR) after SARS-CoV-2 infection. To elucidate this phenomenon, we conducted a longitudinal study involving 47 COVID-19 patients, who were followed up for 12 months. During recruitment, body composition and glucose indices were measured, and heparin blood samples were collected for measuring cytokine production. HOMA-IR was considered an elevated or non-elevated group based on the ratio between HOMA-IR at 12 months and 1 month of convalescence. Those with elevated HOMA-IR had a significantly higher body mass index, body fat percentage, and visceral fat rating and had a lower lean mass and lean/fat mass ratio than their counterparts. During the convalescent period, the elevated HOMA-IR group had lower TNFα, IFNγ, IL-2, IL-10, and granzyme B expression levels but had higher TNFα/IL-10, IFNγ/IL-10, IL-2/IL-10, and granzyme B/IL-10 ratios than the other group. The reduced cytokine production and pro-/anti-inflammatory imbalance in patients with elevated HOMA-IR may suggest immune cell dysfunction toward SARS-CoV-2. Patients with elevated HOMA-IR after SARS-CoV-2 infection may experience an increase in BMI and body fat percentage, leading to increased immune dysfunction and chronic inflammatory condition. A nutritional approach and promotion of physical activity may help reduce HOMA-IR and ameliorate glucose indices in these patients.
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Affiliation(s)
- Rona Kartika
- Doctoral Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jl. Salemba Raya No.6, Jakarta 10430, Indonesia;
- Metabolic Disorder, Cardiovascular, and Aging Research Center, Indonesia Medical Education & Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia, Jl. Salemba Raya No.6, Jakarta 10430, Indonesia; (F.K.); (S.W.); (T.P.); (D.L.T.)
| | - Imam Subekti
- Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jl. P. Diponegoro No. 71, Jakarta 10430, Indonesia;
| | - Farid Kurniawan
- Metabolic Disorder, Cardiovascular, and Aging Research Center, Indonesia Medical Education & Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia, Jl. Salemba Raya No.6, Jakarta 10430, Indonesia; (F.K.); (S.W.); (T.P.); (D.L.T.)
- Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jl. P. Diponegoro No. 71, Jakarta 10430, Indonesia;
| | - Syahidatul Wafa
- Metabolic Disorder, Cardiovascular, and Aging Research Center, Indonesia Medical Education & Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia, Jl. Salemba Raya No.6, Jakarta 10430, Indonesia; (F.K.); (S.W.); (T.P.); (D.L.T.)
- Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jl. P. Diponegoro No. 71, Jakarta 10430, Indonesia;
| | - Tika Pradnjaparamita
- Metabolic Disorder, Cardiovascular, and Aging Research Center, Indonesia Medical Education & Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia, Jl. Salemba Raya No.6, Jakarta 10430, Indonesia; (F.K.); (S.W.); (T.P.); (D.L.T.)
| | - Dicky L. Tahapary
- Metabolic Disorder, Cardiovascular, and Aging Research Center, Indonesia Medical Education & Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia, Jl. Salemba Raya No.6, Jakarta 10430, Indonesia; (F.K.); (S.W.); (T.P.); (D.L.T.)
- Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jl. P. Diponegoro No. 71, Jakarta 10430, Indonesia;
| | - Heri Wibowo
- Metabolic Disorder, Cardiovascular, and Aging Research Center, Indonesia Medical Education & Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia, Jl. Salemba Raya No.6, Jakarta 10430, Indonesia; (F.K.); (S.W.); (T.P.); (D.L.T.)
- Department of Parasitology, Faculty of Medicine, Universitas Indonesia, Jl. Salemba Raya No.6, Jakarta 10430, Indonesia
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15
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Lenz C, Slack MPE, Shea KM, Reinert RR, Taysi BN, Swerdlow DL. Long-Term effects of COVID-19: a review of current perspectives and mechanistic insights. Crit Rev Microbiol 2024; 50:315-328. [PMID: 37074754 DOI: 10.1080/1040841x.2023.2190405] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 02/25/2023] [Indexed: 04/20/2023]
Abstract
Although SARS-CoV-2, responsible for COVID-19, is primarily a respiratory infection, a broad spectrum of cardiac, pulmonary, neurologic, and metabolic complications can occur. More than 50 long-term symptoms of COVID-19 have been described, and as many as 80% of patients may develop ≥1 long-term symptom. To summarize current perspectives of long-term sequelae of COVID-19, we conducted a PubMed search describing the long-term cardiovascular, pulmonary, gastrointestinal, and neurologic effects post-SARS-CoV-2 infection and mechanistic insights and risk factors for the above-mentioned sequelae. Emerging risk factors of long-term sequelae include older age (≥65 years), female sex, Black or Asian race, Hispanic ethnicity, and presence of comorbidities. There is an urgent need to better understand ongoing effects of COVID-19. Prospective studies evaluating long-term effects of COVID-19 in all body systems and patient groups will facilitate appropriate management and assess burden of care. Clinicians should ensure patients are followed up and managed appropriately, especially those in at-risk groups. Healthcare systems worldwide need to develop approaches to follow-up and support patients recovering from COVID-19. Surveillance programs can enhance prevention and treatment efforts for those most vulnerable.
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Affiliation(s)
| | - Mary P E Slack
- Griffith University, School of Medicine and Dentistry, Griffith University Gold Coast campus, Queensland, Australia
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16
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Keck JW, Lacy ME, Bressler S, Blake I, Chukwuma U, Bruce MG. COVID-19 infection and incident diabetes in American Indian and Alaska Native people: a retrospective cohort study. LANCET REGIONAL HEALTH. AMERICAS 2024; 33:100727. [PMID: 38590324 PMCID: PMC11000165 DOI: 10.1016/j.lana.2024.100727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 03/04/2024] [Accepted: 03/18/2024] [Indexed: 04/10/2024]
Abstract
Background Evidence suggests an increased risk of new-onset diabetes following COVID-19 infection. American Indian/Alaska Native (AI/AN) people were disparately impacted by the COVID-19 pandemic and historically have had higher diabetes incidence than other racial/ethnic groups in the US. We measured the association between COVID-19 infection and incident diabetes in AI/AN people. Methods We conducted a retrospective cohort study using de-identified patient data from the Indian Health Service's (IHS) National Patient Information Reporting System. We estimated age-adjusted diabetes incidence rates, incidence rate ratios, and adjusted hazard ratios among three cohorts spanning pre-pandemic (1/1/2018-2/28/2020) and pandemic (3/1/2020-12/31/2021) timeframes: 1) pre-pandemic cohort (1,503,085 individuals); 2) no-COVID-19 pandemic cohort (1,344,339 individuals); and 3) COVID-19 cohort (176,483 individuals). Findings The COVID-19 cohort had an increased hazard of diabetes compared to the no-COVID-19 group (adjusted hazard ratio (aHR) = 1.56; 95% CI: 1.50-1.62) and the pre-pandemic group (aHR = 1.27; 95% CI: 1.22-1.32). The association between COVID-19 infection and new-onset diabetes was stronger in those with severe COVID-19 illness. A sensitivity analysis comparing the COVID-19 cohort to members of other cohorts that had acute upper respiratory infections showed an attenuated but higher risk of new-onset diabetes in those with COVID-19. Interpretation AI/AN people diagnosed with COVID-19 had an elevated risk of a new diabetes diagnosis when compared to the no-COVID-19 group and the pre-pandemic group. The increased diabetes risk in the COVID-19 group remained in a sensitivity analysis that limited the comparator groups to individuals with an AURI diagnosis. Funding US National Institute of Diabetes and Digestive and Kidney Diseases.
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Affiliation(s)
- James W. Keck
- Research Services Department, Alaska Native Tribal Health Consortium, and Centers for Disease Control and Prevention Guest Researcher, Anchorage, AK, USA
| | - Mary E. Lacy
- Department of Epidemiology and Environmental Health, College of Public Health, University of Kentucky, Lexington, KY, USA
| | - Sara Bressler
- Arctic Investigations Program, National Center for Emerging Zoonotic and Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, AK, USA
| | - Ian Blake
- Arctic Investigations Program, National Center for Emerging Zoonotic and Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, AK, USA
| | - Uzo Chukwuma
- Office of Public Health Support, Division of Epidemiology and Disease Prevention, Indian Health Service, Rockville, MD, USA
| | - Michael G. Bruce
- Arctic Investigations Program, National Center for Emerging Zoonotic and Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, AK, USA
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17
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Mone P, Jankauskas SS, Manzi MV, Gambardella J, Coppola A, Kansakar U, Izzo R, Fiorentino G, Lombardi A, Varzideh F, Sorriento D, Trimarco B, Santulli G. Endothelial Extracellular Vesicles Enriched in microRNA-34a Predict New-Onset Diabetes in Coronavirus Disease 2019 (COVID-19) Patients: Novel Insights for Long COVID Metabolic Sequelae. J Pharmacol Exp Ther 2024; 389:34-39. [PMID: 38336381 PMCID: PMC10949163 DOI: 10.1124/jpet.122.001253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Revised: 01/15/2024] [Accepted: 01/23/2024] [Indexed: 02/12/2024] Open
Abstract
Emerging evidence indicates that the relationship between coronavirus disease 2019 (COVID-19) and diabetes is 2-fold: 1) it is known that the presence of diabetes and other metabolic alterations poses a considerably high risk to develop a severe COVID-19; 2) patients who survived a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have an increased risk of developing new-onset diabetes. However, the mechanisms underlying this association are mostly unknown, and there are no reliable biomarkers to predict the development of new-onset diabetes. In the present study, we demonstrate that a specific microRNA (miR-34a) contained in circulating extracellular vesicles released by endothelial cells reliably predicts the risk of developing new-onset diabetes in COVID-19. This association was independent of age, sex, body mass index (BMI), hypertension, dyslipidemia, smoking status, and D-dimer. SIGNIFICANCE STATEMENT: We demonstrate for the first time that a specific microRNA (miR-34a) contained in circulating extracellular vesicles released by endothelial cells is able to reliably predict the risk of developing diabetes after having contracted coronavirus disease 2019 (COVID-19). This association was independent of age, sex, body mass index (BMI), hypertension, dyslipidemia, smoking status, and D-dimer. Our findings are also relevant when considering the emerging importance of post-acute sequelae of COVID-19, with systemic manifestations observed even months after viral negativization (long COVID).
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Affiliation(s)
- Pasquale Mone
- Department of Medicine, Einstein-Sinai Diabetes Research Center, Fleischer Institute for Diabetes and Metabolism, Einstein Institute for Aging Research (P.M., S.S.J., J.G., U.K., A.L., F.V., G.S.) and Department of Molecular Pharmacology, Wilf Family Cardiovascular Research Institute, Einstein Institute for Neuroimmunology and Inflammation (G.S.), Albert Einstein College of Medicine, New York, New York; Department of Advanced Biomedical Sciences, International Translational Research and Medical Education, "Federico II" University, Naples, Italy (M.V.M., J.G., R.I., D.S., B.T., G.S.); Clinica Montevergine, Mercogliano, Avellino (P.M.); and COVID-19 Division, A.O.R.N. Ospedali dei Colli, Naples, Italy (A.C., G.F.)
| | - Stanislovas S Jankauskas
- Department of Medicine, Einstein-Sinai Diabetes Research Center, Fleischer Institute for Diabetes and Metabolism, Einstein Institute for Aging Research (P.M., S.S.J., J.G., U.K., A.L., F.V., G.S.) and Department of Molecular Pharmacology, Wilf Family Cardiovascular Research Institute, Einstein Institute for Neuroimmunology and Inflammation (G.S.), Albert Einstein College of Medicine, New York, New York; Department of Advanced Biomedical Sciences, International Translational Research and Medical Education, "Federico II" University, Naples, Italy (M.V.M., J.G., R.I., D.S., B.T., G.S.); Clinica Montevergine, Mercogliano, Avellino (P.M.); and COVID-19 Division, A.O.R.N. Ospedali dei Colli, Naples, Italy (A.C., G.F.)
| | - Maria Virginia Manzi
- Department of Medicine, Einstein-Sinai Diabetes Research Center, Fleischer Institute for Diabetes and Metabolism, Einstein Institute for Aging Research (P.M., S.S.J., J.G., U.K., A.L., F.V., G.S.) and Department of Molecular Pharmacology, Wilf Family Cardiovascular Research Institute, Einstein Institute for Neuroimmunology and Inflammation (G.S.), Albert Einstein College of Medicine, New York, New York; Department of Advanced Biomedical Sciences, International Translational Research and Medical Education, "Federico II" University, Naples, Italy (M.V.M., J.G., R.I., D.S., B.T., G.S.); Clinica Montevergine, Mercogliano, Avellino (P.M.); and COVID-19 Division, A.O.R.N. Ospedali dei Colli, Naples, Italy (A.C., G.F.)
| | - Jessica Gambardella
- Department of Medicine, Einstein-Sinai Diabetes Research Center, Fleischer Institute for Diabetes and Metabolism, Einstein Institute for Aging Research (P.M., S.S.J., J.G., U.K., A.L., F.V., G.S.) and Department of Molecular Pharmacology, Wilf Family Cardiovascular Research Institute, Einstein Institute for Neuroimmunology and Inflammation (G.S.), Albert Einstein College of Medicine, New York, New York; Department of Advanced Biomedical Sciences, International Translational Research and Medical Education, "Federico II" University, Naples, Italy (M.V.M., J.G., R.I., D.S., B.T., G.S.); Clinica Montevergine, Mercogliano, Avellino (P.M.); and COVID-19 Division, A.O.R.N. Ospedali dei Colli, Naples, Italy (A.C., G.F.)
| | - Antonietta Coppola
- Department of Medicine, Einstein-Sinai Diabetes Research Center, Fleischer Institute for Diabetes and Metabolism, Einstein Institute for Aging Research (P.M., S.S.J., J.G., U.K., A.L., F.V., G.S.) and Department of Molecular Pharmacology, Wilf Family Cardiovascular Research Institute, Einstein Institute for Neuroimmunology and Inflammation (G.S.), Albert Einstein College of Medicine, New York, New York; Department of Advanced Biomedical Sciences, International Translational Research and Medical Education, "Federico II" University, Naples, Italy (M.V.M., J.G., R.I., D.S., B.T., G.S.); Clinica Montevergine, Mercogliano, Avellino (P.M.); and COVID-19 Division, A.O.R.N. Ospedali dei Colli, Naples, Italy (A.C., G.F.)
| | - Urna Kansakar
- Department of Medicine, Einstein-Sinai Diabetes Research Center, Fleischer Institute for Diabetes and Metabolism, Einstein Institute for Aging Research (P.M., S.S.J., J.G., U.K., A.L., F.V., G.S.) and Department of Molecular Pharmacology, Wilf Family Cardiovascular Research Institute, Einstein Institute for Neuroimmunology and Inflammation (G.S.), Albert Einstein College of Medicine, New York, New York; Department of Advanced Biomedical Sciences, International Translational Research and Medical Education, "Federico II" University, Naples, Italy (M.V.M., J.G., R.I., D.S., B.T., G.S.); Clinica Montevergine, Mercogliano, Avellino (P.M.); and COVID-19 Division, A.O.R.N. Ospedali dei Colli, Naples, Italy (A.C., G.F.)
| | - Raffaele Izzo
- Department of Medicine, Einstein-Sinai Diabetes Research Center, Fleischer Institute for Diabetes and Metabolism, Einstein Institute for Aging Research (P.M., S.S.J., J.G., U.K., A.L., F.V., G.S.) and Department of Molecular Pharmacology, Wilf Family Cardiovascular Research Institute, Einstein Institute for Neuroimmunology and Inflammation (G.S.), Albert Einstein College of Medicine, New York, New York; Department of Advanced Biomedical Sciences, International Translational Research and Medical Education, "Federico II" University, Naples, Italy (M.V.M., J.G., R.I., D.S., B.T., G.S.); Clinica Montevergine, Mercogliano, Avellino (P.M.); and COVID-19 Division, A.O.R.N. Ospedali dei Colli, Naples, Italy (A.C., G.F.)
| | - Giuseppe Fiorentino
- Department of Medicine, Einstein-Sinai Diabetes Research Center, Fleischer Institute for Diabetes and Metabolism, Einstein Institute for Aging Research (P.M., S.S.J., J.G., U.K., A.L., F.V., G.S.) and Department of Molecular Pharmacology, Wilf Family Cardiovascular Research Institute, Einstein Institute for Neuroimmunology and Inflammation (G.S.), Albert Einstein College of Medicine, New York, New York; Department of Advanced Biomedical Sciences, International Translational Research and Medical Education, "Federico II" University, Naples, Italy (M.V.M., J.G., R.I., D.S., B.T., G.S.); Clinica Montevergine, Mercogliano, Avellino (P.M.); and COVID-19 Division, A.O.R.N. Ospedali dei Colli, Naples, Italy (A.C., G.F.)
| | - Angela Lombardi
- Department of Medicine, Einstein-Sinai Diabetes Research Center, Fleischer Institute for Diabetes and Metabolism, Einstein Institute for Aging Research (P.M., S.S.J., J.G., U.K., A.L., F.V., G.S.) and Department of Molecular Pharmacology, Wilf Family Cardiovascular Research Institute, Einstein Institute for Neuroimmunology and Inflammation (G.S.), Albert Einstein College of Medicine, New York, New York; Department of Advanced Biomedical Sciences, International Translational Research and Medical Education, "Federico II" University, Naples, Italy (M.V.M., J.G., R.I., D.S., B.T., G.S.); Clinica Montevergine, Mercogliano, Avellino (P.M.); and COVID-19 Division, A.O.R.N. Ospedali dei Colli, Naples, Italy (A.C., G.F.)
| | - Fahimeh Varzideh
- Department of Medicine, Einstein-Sinai Diabetes Research Center, Fleischer Institute for Diabetes and Metabolism, Einstein Institute for Aging Research (P.M., S.S.J., J.G., U.K., A.L., F.V., G.S.) and Department of Molecular Pharmacology, Wilf Family Cardiovascular Research Institute, Einstein Institute for Neuroimmunology and Inflammation (G.S.), Albert Einstein College of Medicine, New York, New York; Department of Advanced Biomedical Sciences, International Translational Research and Medical Education, "Federico II" University, Naples, Italy (M.V.M., J.G., R.I., D.S., B.T., G.S.); Clinica Montevergine, Mercogliano, Avellino (P.M.); and COVID-19 Division, A.O.R.N. Ospedali dei Colli, Naples, Italy (A.C., G.F.)
| | - Daniela Sorriento
- Department of Medicine, Einstein-Sinai Diabetes Research Center, Fleischer Institute for Diabetes and Metabolism, Einstein Institute for Aging Research (P.M., S.S.J., J.G., U.K., A.L., F.V., G.S.) and Department of Molecular Pharmacology, Wilf Family Cardiovascular Research Institute, Einstein Institute for Neuroimmunology and Inflammation (G.S.), Albert Einstein College of Medicine, New York, New York; Department of Advanced Biomedical Sciences, International Translational Research and Medical Education, "Federico II" University, Naples, Italy (M.V.M., J.G., R.I., D.S., B.T., G.S.); Clinica Montevergine, Mercogliano, Avellino (P.M.); and COVID-19 Division, A.O.R.N. Ospedali dei Colli, Naples, Italy (A.C., G.F.)
| | - Bruno Trimarco
- Department of Medicine, Einstein-Sinai Diabetes Research Center, Fleischer Institute for Diabetes and Metabolism, Einstein Institute for Aging Research (P.M., S.S.J., J.G., U.K., A.L., F.V., G.S.) and Department of Molecular Pharmacology, Wilf Family Cardiovascular Research Institute, Einstein Institute for Neuroimmunology and Inflammation (G.S.), Albert Einstein College of Medicine, New York, New York; Department of Advanced Biomedical Sciences, International Translational Research and Medical Education, "Federico II" University, Naples, Italy (M.V.M., J.G., R.I., D.S., B.T., G.S.); Clinica Montevergine, Mercogliano, Avellino (P.M.); and COVID-19 Division, A.O.R.N. Ospedali dei Colli, Naples, Italy (A.C., G.F.)
| | - Gaetano Santulli
- Department of Medicine, Einstein-Sinai Diabetes Research Center, Fleischer Institute for Diabetes and Metabolism, Einstein Institute for Aging Research (P.M., S.S.J., J.G., U.K., A.L., F.V., G.S.) and Department of Molecular Pharmacology, Wilf Family Cardiovascular Research Institute, Einstein Institute for Neuroimmunology and Inflammation (G.S.), Albert Einstein College of Medicine, New York, New York; Department of Advanced Biomedical Sciences, International Translational Research and Medical Education, "Federico II" University, Naples, Italy (M.V.M., J.G., R.I., D.S., B.T., G.S.); Clinica Montevergine, Mercogliano, Avellino (P.M.); and COVID-19 Division, A.O.R.N. Ospedali dei Colli, Naples, Italy (A.C., G.F.)
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18
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Conte C, Cipponeri E, Roden M. Diabetes Mellitus, Energy Metabolism, and COVID-19. Endocr Rev 2024; 45:281-308. [PMID: 37934800 PMCID: PMC10911957 DOI: 10.1210/endrev/bnad032] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 08/30/2023] [Accepted: 11/01/2023] [Indexed: 11/09/2023]
Abstract
Obesity, diabetes mellitus (mostly type 2), and COVID-19 show mutual interactions because they are not only risk factors for both acute and chronic COVID-19 manifestations, but also because COVID-19 alters energy metabolism. Such metabolic alterations can lead to dysglycemia and long-lasting effects. Thus, the COVID-19 pandemic has the potential for a further rise of the diabetes pandemic. This review outlines how preexisting metabolic alterations spanning from excess visceral adipose tissue to hyperglycemia and overt diabetes may exacerbate COVID-19 severity. We also summarize the different effects of SARS-CoV-2 infection on the key organs and tissues orchestrating energy metabolism, including adipose tissue, liver, skeletal muscle, and pancreas. Last, we provide an integrative view of the metabolic derangements that occur during COVID-19. Altogether, this review allows for better understanding of the metabolic derangements occurring when a fire starts from a small flame, and thereby help reducing the impact of the COVID-19 pandemic.
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Affiliation(s)
- Caterina Conte
- Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, Rome 00166, Italy
- Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, Milan 20099, Italy
| | - Elisa Cipponeri
- Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, Milan 20099, Italy
| | - Michael Roden
- Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf 40225, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University Düsseldorf, Düsseldorf 40225, Germany
- German Center for Diabetes Research, Partner Düsseldorf, Neuherberg 85764, Germany
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19
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Harris A, Creecy A, Awosanya OD, McCune T, Ozanne MV, Toepp AJ, Kacena MA, Qiao X. SARS-CoV-2 and its Multifaceted Impact on Bone Health: Mechanisms and Clinical Evidence. Curr Osteoporos Rep 2024; 22:135-145. [PMID: 38236510 PMCID: PMC10912131 DOI: 10.1007/s11914-023-00843-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/15/2023] [Indexed: 01/19/2024]
Abstract
PURPOSE OF REVIEW SARS-CoV-2 infection, the culprit of the COVID-19 pandemic, has been associated with significant long-term effects on various organ systems, including bone health. This review explores the current understanding of the impacts of SARS-CoV-2 infection on bone health and its potential long-term consequences. RECENT FINDINGS As part of the post-acute sequelae of SARS-CoV-2 infection, bone health changes are affected by COVID-19 both directly and indirectly, with multiple potential mechanisms and risk factors involved. In vitro and preclinical studies suggest that SARS-CoV-2 may directly infect bone marrow cells, leading to alterations in bone structure and osteoclast numbers. The virus can also trigger a robust inflammatory response, often referred to as a "cytokine storm", which can stimulate osteoclast activity and contribute to bone loss. Clinical evidence suggests that SARS-CoV-2 may lead to hypocalcemia, altered bone turnover markers, and a high prevalence of vertebral fractures. Furthermore, disease severity has been correlated with a decrease in bone mineral density. Indirect effects of SARS-CoV-2 on bone health, mediated through muscle weakness, mechanical unloading, nutritional deficiencies, and corticosteroid use, also contribute to the long-term consequences. The interplay of concurrent conditions such as diabetes, obesity, and kidney dysfunction with SARS-CoV-2 infection further complicates the disease's impact on bone health. SARS-CoV-2 infection directly and indirectly affects bone health, leading to potential long-term consequences. This review article is part of a series of multiple manuscripts designed to determine the utility of using artificial intelligence for writing scientific reviews.
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Affiliation(s)
- Alexander Harris
- Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Amy Creecy
- Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Olatundun D Awosanya
- Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Thomas McCune
- Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA, USA
- Division of Nephrology, Eastern Virginia Medical School, Norfolk, VA, USA
| | - Marie V Ozanne
- Department of Mathematics and Statistics, Mount Holyoke College, South Hadley, MA, USA
| | - Angela J Toepp
- Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA, USA
- Enterprise Analytics, Sentara Health, Virginia Beach, VA, USA
| | - Melissa A Kacena
- Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
- Richard L. Roudebush VA Medical Center, Indianapolis, IN, USA.
| | - Xian Qiao
- Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA, USA.
- SMG Pulmonary, Critical Care, and Sleep Specialists, Norfolk, VA, USA.
- Division of Pulmonary and Critical Care Medicine, Eastern Virginia Medical School, Norfolk, VA, USA.
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20
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Xu X, Shi Z, Zhou L, Lin J, Atlantis E, Chen X, Hussain A, Wang Y, Wang Y. Impact of COVID-19 on risks and deaths of non-communicable diseases in the Western Pacific region. THE LANCET REGIONAL HEALTH. WESTERN PACIFIC 2024; 43:100795. [PMID: 38456087 PMCID: PMC10920048 DOI: 10.1016/j.lanwpc.2023.100795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 04/08/2023] [Accepted: 05/04/2023] [Indexed: 03/09/2024]
Abstract
Countries and areas in the Western Pacific region (WPR) experienced the COVID-19 pandemic and took various preventive measures, which affected non-communicable diseases (NCDs) risks and mortality. Due to differences in COVID-19 prevention measures and other characteristics such as culture, religions, political systems, socioeconomic development, lifestyles, and health care systems, the effects of COVID-19 on NCDs varied greatly among WPR countries. Most countries had an increased all-cause and NCDs mortality during the pandemic, but some developed countries, including New Zealand, Singapore and Australia reported decreased mortality. The pandemic and the preventive measures increased NCD risk factors including unhealthy diet, lack of physical activity and sleep disorders. The effects varied by socioeconomic status and health conditions. COVID-19 related stress, food shortages, and confined lifestyle had immediate detrimental effects on NCDs, and also affected pregnancy outcomes with long-term effects on NCDs risks in coming years.
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Affiliation(s)
- Xiaoyue Xu
- School of Population Heath, University of New South Wales, Australia
| | - Zumin Shi
- Human Nutrition Department, College of Health Sciences, QU Health, Qatar University, Doha, 2713, Qatar
| | - Lihui Zhou
- School of Public Health, Tianjin Medical University, Tianjin, People's Republic of China
| | - Jing Lin
- School of Public Health, Tianjin Medical University, Tianjin, People's Republic of China
| | - Evan Atlantis
- School of Health Sciences, Western Sydney University, Penrith, New South Wales, Australia
- Discipline of Medicine, Nepean Clinical School, Faculty of Medicine and Health, The University of Sydney, Nepean, New South Wales, Australia
| | - Xinguang Chen
- The First Affiliated Hospital of Xi'an Jiaotong University Public Health Institute, Global Health Institute, School of Public Health, International Obesity and Metabolic Disease Research Center, Xi’an Jiaotong University, Xi’an 710061, People’s Republic of China
| | - Akhtar Hussain
- Faculty of Health Sciences, Nord University, Bodø, 8049, Norway
- International Diabetes Federation, 166 Chaussee de La Hulpe, B-1170, Brussels, Belgium
| | - Youfa Wang
- The First Affiliated Hospital of Xi'an Jiaotong University Public Health Institute, Global Health Institute, School of Public Health, International Obesity and Metabolic Disease Research Center, Xi’an Jiaotong University, Xi’an 710061, People’s Republic of China
| | - Yaogang Wang
- School of Public Health, Tianjin Medical University, Tianjin, People's Republic of China
- National Institute of Health Data Science at Peking University, Peking University, Beijing, People's Republic of China
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21
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Creecy A, Awosanya OD, Harris A, Qiao X, Ozanne M, Toepp AJ, Kacena MA, McCune T. COVID-19 and Bone Loss: A Review of Risk Factors, Mechanisms, and Future Directions. Curr Osteoporos Rep 2024; 22:122-134. [PMID: 38221578 PMCID: PMC10912142 DOI: 10.1007/s11914-023-00842-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/15/2023] [Indexed: 01/16/2024]
Abstract
PURPOSE OF REVIEW SARS-CoV-2 drove the catastrophic global phenomenon of the COVID-19 pandemic resulting in a multitude of systemic health issues, including bone loss. The purpose of this review is to summarize recent findings related to bone loss and potential mechanisms. RECENT FINDINGS The early clinical evidence indicates an increase in vertebral fractures, hypocalcemia, vitamin D deficiencies, and a loss in BMD among COVID-19 patients. Additionally, lower BMD is associated with more severe SARS-CoV-2 infection. Preclinical models have shown bone loss and increased osteoclastogenesis. The bone loss associated with SARS-CoV-2 infection could be the result of many factors that directly affect the bone such as higher inflammation, activation of the NLRP3 inflammasome, recruitment of Th17 cells, the hypoxic environment, and changes in RANKL/OPG signaling. Additionally, SARS-CoV-2 infection can exert indirect effects on the skeleton, as mechanical unloading may occur with severe disease (e.g., bed rest) or with BMI loss and muscle wasting that has also been shown to occur with SARS-CoV-2 infection. Muscle wasting can also cause systemic issues that may influence the bone. Medications used to treat SARS-CoV-2 infection also have a negative effect on the bone. Lastly, SARS-CoV-2 infection may also worsen conditions such as diabetes and negatively affect kidney function, all of which could contribute to bone loss and increased fracture risk. SARS-CoV-2 can negatively affect the bone through multiple direct and indirect mechanisms. Future work will be needed to determine what patient populations are at risk of COVID-19-related increases in fracture risk, the mechanisms behind bone loss, and therapeutic options. This review article is part of a series of multiple manuscripts designed to determine the utility of using artificial intelligence for writing scientific reviews.
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Affiliation(s)
- Amy Creecy
- Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Olatundun D Awosanya
- Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Alexander Harris
- Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Xian Qiao
- Critical Care, and Sleep Specialists, SMG Pulmonary, Norfolk, VA, USA
- Division of Pulmonary and Critical Care Medicine, Eastern Virginia Medical School, Norfolk, VA, USA
- Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA, USA
| | - Marie Ozanne
- Department of Mathematics and Statistics, Mount Holyoke College, South Hadley, MA, USA
| | - Angela J Toepp
- Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA, USA
- Enterprise Analytics, Sentara Health, Virginia Beach, VA, USA
| | - Melissa A Kacena
- Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
- Richard L. Roudebush VA Medical Center, Indianapolis, IN, USA.
| | - Thomas McCune
- Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA, USA.
- Division of Nephrology, Eastern Virginia Medical School, Norfolk, VA, USA.
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22
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Lai Z, Pu T, Li J, Bai F, Wu L, Tang Y. Visual analysis of hotspots and trends in long COVID research based on bibliometric. Heliyon 2024; 10:e24053. [PMID: 38293444 PMCID: PMC10827472 DOI: 10.1016/j.heliyon.2024.e24053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Revised: 11/23/2023] [Accepted: 01/03/2024] [Indexed: 02/01/2024] Open
Abstract
After severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a series of symptoms may persist for a long time, which is now called long COVID. It was found that long COVID can affect all patients with COVID-19. Therefore, long COVID has become a hot topic. In this study, we used the WOS database as a sample data source to conduct a bibliometric and visual analysis of 1765 long COVID articles over the past three years through VOSviewer and R package. The results show that countries/authors in Europe and The United States of America contribute most of the articles, and their cooperation is also the most active. Keyword co-occurrence identified four clusters, with important topics including the mechanism, clinical symptoms, epidemiological characteristics, and management/treatment of long COVID. Themes such as "cognitive impairment", "endothelial dysfunction", "diagnosis", and "biomarkers" are likely to be the focus of new attention in the coming period. In addition, we put forward the possible research opportunities on long COVID for researchers and practitioners to facilitate future research.
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Affiliation(s)
- Zongqiang Lai
- The Pharmaceutical Department, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, PR China
| | - Tao Pu
- Department of Adolescent Gynecology, Shenzhen Children's Hospital, Shenzhen, Guangdong, PR China
| | - Jun Li
- The Pharmaceutical Department, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, PR China
| | - Facheng Bai
- The Pharmaceutical Department, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, PR China
| | - Lining Wu
- The Pharmaceutical Department, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, PR China
| | - Yunxia Tang
- The Pharmaceutical Department, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, PR China
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23
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Rosenbauer J, Stahl-Pehe A, Baechle C, Lanzinger S, Kamrath C, Kuß O, Holl RW. Spatiotemporal association between COVID-19 incidence and type 1 diabetes incidence among children and adolescents: a register-based ecological study in Germany. Front Endocrinol (Lausanne) 2024; 14:1287354. [PMID: 38234422 PMCID: PMC10791930 DOI: 10.3389/fendo.2023.1287354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 12/04/2023] [Indexed: 01/19/2024] Open
Abstract
Objective Studies have shown an increased incidence of pediatric type 1 diabetes during the COVID-19 pandemic, but the detailed role of SARS-CoV-2 infection in the incidence increase in type 1 diabetes remains unclear. We investigated the spatiotemporal association of pediatric type 1 diabetes and COVID-19 incidence at the district level in Germany. Methods For the period from March 2020 to June 2022, nationwide data on incident type 1 diabetes among children and adolescents aged <20 years and daily documented COVID-19 infections in the total population were obtained from the German Diabetes Prospective Follow-up Registry and the Robert Koch Institute, respectively. Data were aggregated at district level and seven time periods related to COVID-19 pandemic waves. Spatiotemporal associations between indirectly standardized incidence rates of type 1 diabetes and COVID-19 were analyzed by Spearman correlation and Bayesian spatiotemporal conditional autoregressive Poisson models. Results Standardized incidence ratios of type 1 diabetes and COVID-19 in the pandemic period were not significantly correlated across districts and time periods. A doubling of the COVID-19 incidence rate was not associated with a significant increase in the incidence rate of type 1 diabetes (relative risk 1.006, 95% CI 0.987; 1.019). Conclusion Our findings based on data from the pandemic period indirectly indicate that a causal relationship between SARS-COV-2 infection and type 1 diabetes among children and adolescents is unlikely.
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Affiliation(s)
- Joachim Rosenbauer
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), Munich, Germany
| | - Anna Stahl-Pehe
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), Munich, Germany
| | - Christina Baechle
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), Munich, Germany
| | - Stefanie Lanzinger
- German Center for Diabetes Research (DZD), Munich, Germany
- Institute of Epidemiology and Medical Biometry, Central Institute for Biomedical Technology (ZIBMT), Ulm University, Ulm, Germany
| | - Clemens Kamrath
- Center of Child and Adolescent Medicine, Justus Liebig University Giessen, Giessen, Germany
| | - Oliver Kuß
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), Munich, Germany
- Centre for Health and Society, Medical Faculty and University Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Reinhard W. Holl
- German Center for Diabetes Research (DZD), Munich, Germany
- Institute of Epidemiology and Medical Biometry, Central Institute for Biomedical Technology (ZIBMT), Ulm University, Ulm, Germany
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24
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Izzo R, Pacella D, Trimarco V, Manzi MV, Lombardi A, Piccinocchi R, Gallo P, Esposito G, Lembo M, Piccinocchi G, Morisco C, Santulli G, Trimarco B. Incidence of type 2 diabetes before and during the COVID-19 pandemic in Naples, Italy: a longitudinal cohort study. EClinicalMedicine 2023; 66:102345. [PMID: 38143804 PMCID: PMC10746394 DOI: 10.1016/j.eclinm.2023.102345] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 10/31/2023] [Accepted: 11/15/2023] [Indexed: 12/26/2023] Open
Abstract
Background The association of COVID-19 with the development of new-onset diabetes has been recently investigated by several groups, yielding controversial results. Population studies currently available in the literature are mostly focused on type 1 diabetes (T1D), comparing patients with a SARS-CoV-2 positive test to individuals without COVID-19, especially in paediatric populations. In this study, we sought to determine the incidence of type 2 diabetes (T2D) before and during the COVID-19 pandemic. Methods In this longitudinal cohort study, we analysed a cohort followed up over a 6-year period using an Interrupted Time Series approach, i.e. 3-years before and 3-years during the COVID-19 pandemic. We analysed data obtained from >200,000 adults in Naples (Italy) from January 1st 2017 to December 31st 2022. In this manner, we had the opportunity to compare the incidence of newly diagnosed T2D before (2017-2019) and during (2020-2022) the COVID-19 pandemic. The key inclusion criteria were age >18-year-old and data availability for the period of observation; patients with a diagnosis of diabetes obtained before 2017 were excluded. The main outcome of the study was the new diagnosis of T2D, as defined by the International Classification of Diseases 10 (ICD-X), including prescription of antidiabetic therapies for more than 30 days. Findings A total of 234,956 subjects were followed-up for at least 3-years before or 3-years during the COVID-19 pandemic and were included in the study; among these, 216,498 were analysed in the pre-pandemic years and 216,422 in the pandemic years. The incidence rate of T2D was 4.85 (95% CI, 4.68-5.02) per 1000 person-years in the period 2017-2019, vs 12.21 (95% CI, 11.94-12.48) per 1000 person-years in 2020-2022, with an increase of about twice and a half. Moreover, the doubling time of the number of new diagnoses of T2D estimated by unadjusted Poisson model was 97.12 (95% CI, 40.51-153.75) months in the prepandemic period vs 23.13 (95% CI, 16.02-41.59) months during the COVID-19 pandemic. Interestingly, these findings were also confirmed when examining patients with prediabetes. Interpretation Our data from this 6-year study on more than 200,000 adult participants indicate that the incidence of T2D was significantly higher during the pandemic compared to the pre-COVID-19 phase. As a consequence, the epidemiology of the disease may change in terms of rates of outcomes as well as public health costs. COVID-19 survivors, especially patients with prediabetes, may require specific clinical programs to prevent T2D. Funding The US National Institutes of Health (NIH: NIDDK, NHLBI, NCATS), Diabetes Action Research and Education Foundation, Weill-Caulier and Hirschl Trusts.
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Affiliation(s)
- Raffaele Izzo
- Department of Advanced Biomedical Sciences, “Federico II” University, Naples, Italy
| | - Daniela Pacella
- Department of Public Health, “Federico II” University, Naples, Italy
| | - Valentina Trimarco
- Department of Neuroscience, Reproductive Sciences, and Dentistry, “Federico II” University, Naples, Italy
| | - Maria Virginia Manzi
- Department of Advanced Biomedical Sciences, “Federico II” University, Naples, Italy
| | - Angela Lombardi
- Department of Microbiology and Immunology, Fleischer Institute for Diabetes and Metabolism (FIDAM), Albert Einstein College of Medicine, New York City, NY, USA
| | | | - Paola Gallo
- Department of Public Health, “Federico II” University, Naples, Italy
| | - Giovanni Esposito
- Department of Advanced Biomedical Sciences, “Federico II” University, Naples, Italy
| | - Maria Lembo
- Department of Advanced Biomedical Sciences, “Federico II” University, Naples, Italy
| | - Gaetano Piccinocchi
- COMEGEN Primary Care Physicians Cooperative, Italian Society of General Medicine (SIMG), Naples, Italy
| | - Carmine Morisco
- Department of Advanced Biomedical Sciences, “Federico II” University, Naples, Italy
- International Translational Research and Medical Education (ITME) Consortium, Academic Research Unit, Naples, Italy
- Italian Society for Cardiovascular Prevention (SIPREC), Rome, Italy
| | - Gaetano Santulli
- Department of Advanced Biomedical Sciences, “Federico II” University, Naples, Italy
- International Translational Research and Medical Education (ITME) Consortium, Academic Research Unit, Naples, Italy
- Department of Medicine, Wilf Family Cardiovascular Research Institute, Einstein-Mount Sinai Diabetes Research Center (ES-DRC), Albert Einstein College of Medicine, New York City, NY, USA
- Department of Molecular Pharmacology, Einstein Institute for Aging Research, Institute for Neuroimmunology and Inflammation (INI), Albert Einstein College of Medicine, New York City, NY, USA
| | - Bruno Trimarco
- Department of Advanced Biomedical Sciences, “Federico II” University, Naples, Italy
- International Translational Research and Medical Education (ITME) Consortium, Academic Research Unit, Naples, Italy
- Italian Society for Cardiovascular Prevention (SIPREC), Rome, Italy
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di Filippo L, Frara S, Nannipieri F, Cotellessa A, Locatelli M, Rovere Querini P, Giustina A. Low Vitamin D Levels Are Associated With Long COVID Syndrome in COVID-19 Survivors. J Clin Endocrinol Metab 2023; 108:e1106-e1116. [PMID: 37051747 PMCID: PMC10505553 DOI: 10.1210/clinem/dgad207] [Citation(s) in RCA: 48] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 03/14/2023] [Accepted: 04/11/2023] [Indexed: 04/14/2023]
Abstract
CONTEXT Long COVID is an emerging syndrome affecting 50% to 70% of COVID-19 survivors that still lacks predicting factors. OBJECTIVE Due to the extraskeletal effects of vitamin D, we retrospectively assessed the association between 25(OH) vitamin D levels and long COVID in COVID-19 survivors 6 months after hospitalization. METHODS Long COVID was defined according to NICE guidelines. Fifty long COVID and 50 non-long-COVID subjects matched on a 1:1 basis were enrolled from an outpatient clinic post-COVID cohort seen from August to November 2020. Therapies/comorbidities affecting calcium/vitamin D/bone metabolism, and/or admission to the intensive care unit during hospitalization were exclusion criteria. 25(OH) Vitamin D was measured at hospital admission and 6 months after discharge. RESULTS We observed lower 25(OH) vitamin D levels, evaluated at follow-up, in subjects with long COVID than those without (20.1 vs 23.2 ng/mL, P = .03). Regarding the affected health areas evaluated in the entire cohort, we observed lower 25(OH) vitamin D levels in those with neurocognitive symptoms at follow-up (n = 7) than those without (n = 93) (14.6 vs 20.6 ng/mL, P = .042). In patients presenting vitamin D deficiency (<20 ng/mL), both at admission and at follow-up (n = 42), those affected by long COVID (n = 22) presented lower 25(OH) vitamin D levels at follow-up than those not affected (n = 20) (12.7 vs 15.2 ng/mL, P = .041). In multiple regression analyses, lower 25(OH) vitamin D levels at follow-up were the only variable significantly associated with long COVID in our cohort (P = .008, OR 1.09, CI 1.01-1.16). CONCLUSION COVID-19 survivors with long COVID have lower 25(OH) vitamin D levels than matched patients without long COVID. Our data suggest that vitamin D levels should be evaluated in COVID-19 patients after hospital discharge. The role of vitamin D supplementation as a preventive strategy of COVID-19 sequelae should be tested in randomized controlled trials.
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Affiliation(s)
- Luigi di Filippo
- Institute of Endocrine and Metabolic Sciences, Università Vita-Salute San Raffaele, IRCCS Ospedale San Raffaele, Milan 20132, Italy
| | - Stefano Frara
- Institute of Endocrine and Metabolic Sciences, Università Vita-Salute San Raffaele, IRCCS Ospedale San Raffaele, Milan 20132, Italy
| | | | - Alice Cotellessa
- Laboratory Medicine Service, IRCCS Ospedale San Raffaele, Milan 20132, Italy
| | - Massimo Locatelli
- Laboratory Medicine Service, IRCCS Ospedale San Raffaele, Milan 20132, Italy
| | - Patrizia Rovere Querini
- Division of Immunology, Transplantation & Infectious Diseases, Università Vita-Salute San Raffaele, IRCCS Ospedale San Raffaele, Milan 20132, Italy
| | - Andrea Giustina
- Institute of Endocrine and Metabolic Sciences, Università Vita-Salute San Raffaele, IRCCS Ospedale San Raffaele, Milan 20132, Italy
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Bellia C, Andreadi A, D’Ippolito I, Scola L, Barraco S, Meloni M, Lauro D, Bellia A. Prevalence and risk of new-onset diabetes mellitus after COVID-19: a systematic review and meta-analysis. Front Endocrinol (Lausanne) 2023; 14:1215879. [PMID: 37732118 PMCID: PMC10507325 DOI: 10.3389/fendo.2023.1215879] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Accepted: 08/16/2023] [Indexed: 09/22/2023] Open
Abstract
Aims After the acute phase of SARS-CoV-2 infection, the onset of glycemic impairment and diabetes have been reported. Nevertheless, the exact burden of glycemic impairment and diabetes after COVID-19 has not been clearly described. Materials and methods Electronic search was run in Pubmed (MEDLINE), Web of Science, Scopus, and ClinicalTrial.org for reports published from database inception to September 2022. We included observational studies reporting quantitative data on diabetes prevalence or its onset in subjects with a history of SARS-CoV-2 infection from at least 60 days. Risk of bias was assessed by the JBI's critical appraisal checklist. Random effect model was used to calculate pooled data. The review protocol was registered on PROSPERO (CRD42022310722). Results Among 1,630 records screened, 20 studies were included in the analysis. The mean or median age of participants ranged from ~ 35 to 64 years, with a percentage of males ranging from 28% to 80%. Only two studies were considered at low risk of bias. The estimate of diabetes prevalence, calculated on a total of 320,948 participants pooled with 38,731 cases, was 16% (95%CI: 11-22%). The estimate of proportion of incident cases of diabetes was 1.6% (95%CI: 0.8-2.7%). Subgroup analysis showed that previous hospitalization increased the prevalence of diabetes and the proportion of incident cases. Conclusion Diabetes is common in individuals who have experienced SARS-CoV-2 infection, especially if they required hospitalization. This data may be helpful to screen for diabetes and manage its complications in individuals who experienced COVID-19. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022310722, identifier CRD42022310722.
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Affiliation(s)
- Chiara Bellia
- Department of Biomedicine, Neurosciences, and Advanced Diagnostics, University of Palermo, Palermo, Italy
- Transfusion Medicine Unit, University Hospital “Paolo Giaccone”, Palermo, Italy
| | - Aikaterini Andreadi
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- Division of Endocrinology and Diabetes, Fondazione Policlinico Tor Vergata, Rome, Italy
| | - Ilenia D’Ippolito
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- Division of Endocrinology and Diabetes, Fondazione Policlinico Tor Vergata, Rome, Italy
| | - Letizia Scola
- Department of Biomedicine, Neurosciences, and Advanced Diagnostics, University of Palermo, Palermo, Italy
- Transfusion Medicine Unit, University Hospital “Paolo Giaccone”, Palermo, Italy
| | - Sonia Barraco
- Division of Endocrinology and Diabetes, Fondazione Policlinico Tor Vergata, Rome, Italy
| | - Marco Meloni
- Division of Endocrinology and Diabetes, Fondazione Policlinico Tor Vergata, Rome, Italy
| | - Davide Lauro
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- Division of Endocrinology and Diabetes, Fondazione Policlinico Tor Vergata, Rome, Italy
| | - Alfonso Bellia
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- Division of Endocrinology and Diabetes, Fondazione Policlinico Tor Vergata, Rome, Italy
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Perakakis N, Harb H, Hale BG, Varga Z, Steenblock C, Kanczkowski W, Alexaki VI, Ludwig B, Mirtschink P, Solimena M, Toepfner N, Zeissig S, Gado M, Abela IA, Beuschlein F, Spinas GA, Cavelti-Weder C, Gerber PA, Huber M, Trkola A, Puhan MA, Wong WWL, Linkermann A, Mohan V, Lehnert H, Nawroth P, Chavakis T, Mingrone G, Wolfrum C, Zinkernagel AS, Bornstein SR. Mechanisms and clinical relevance of the bidirectional relationship of viral infections with metabolic diseases. Lancet Diabetes Endocrinol 2023; 11:675-693. [PMID: 37524103 DOI: 10.1016/s2213-8587(23)00154-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 05/09/2023] [Accepted: 05/19/2023] [Indexed: 08/02/2023]
Abstract
Viruses have been present during all evolutionary steps on earth and have had a major effect on human history. Viral infections are still among the leading causes of death. Another public health concern is the increase of non-communicable metabolic diseases in the last four decades. In this Review, we revisit the scientific evidence supporting the presence of a strong bidirectional feedback loop between several viral infections and metabolic diseases. We discuss how viruses might lead to the development or progression of metabolic diseases and conversely, how metabolic diseases might increase the severity of a viral infection. Furthermore, we discuss the clinical relevance of the current evidence on the relationship between viral infections and metabolic disease and the present and future challenges that should be addressed by the scientific community and health authorities.
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Affiliation(s)
- Nikolaos Perakakis
- Department of Internal Medicine III, Technische Universität Dresden, Dresden 01307, Germany; Paul Langerhans Institute Dresden, Helmholtz Munich, Technische Universität Dresden, Dresden 01307, Germany; German Center for Diabetes Research, Neuherberg, Germany.
| | - Hani Harb
- Medical Microbiology and Virology, Technische Universität Dresden, Dresden 01307, Germany
| | - Benjamin G Hale
- Institute of Medical Virology, University of Zürich, Zürich, Switzerland
| | - Zsuzsanna Varga
- Department of Pathology and Molecular Pathology, University of Zürich, Zürich, Switzerland
| | - Charlotte Steenblock
- Department of Internal Medicine III, Technische Universität Dresden, Dresden 01307, Germany
| | - Waldemar Kanczkowski
- Department of Internal Medicine III, Technische Universität Dresden, Dresden 01307, Germany
| | - Vasileia Ismini Alexaki
- Institute for Institute of Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden, Dresden 01307, Germany
| | - Barbara Ludwig
- Department of Internal Medicine III, Technische Universität Dresden, Dresden 01307, Germany; Paul Langerhans Institute Dresden, Helmholtz Munich, Technische Universität Dresden, Dresden 01307, Germany; Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden 01307, Germany; German Center for Diabetes Research, Neuherberg, Germany
| | - Peter Mirtschink
- Institute for Institute of Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden, Dresden 01307, Germany
| | - Michele Solimena
- Paul Langerhans Institute Dresden, Helmholtz Munich, Technische Universität Dresden, Dresden 01307, Germany; Department of Molecular Diabetology, Technische Universität Dresden, Dresden 01307, Germany; German Center for Diabetes Research, Neuherberg, Germany
| | - Nicole Toepfner
- Department of Pediatrics, Technische Universität Dresden, Dresden 01307, Germany
| | - Sebastian Zeissig
- Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden 01307, Germany; Department of Medicine I, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden 01307, Germany
| | - Manuel Gado
- Department of Internal Medicine III, Technische Universität Dresden, Dresden 01307, Germany; Paul Langerhans Institute Dresden, Helmholtz Munich, Technische Universität Dresden, Dresden 01307, Germany; German Center for Diabetes Research, Neuherberg, Germany
| | - Irene Alma Abela
- Institute of Medical Virology, University of Zürich, Zürich, Switzerland; Department of Infectious Diseases and Hospital Epidemiology, University of Zürich, Zürich, Switzerland
| | - Felix Beuschlein
- Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zürich, University of Zürich, Zürich, Switzerland; Medizinische Klinik und Poliklinik IV, Klinikum der Universität, Ludwig-Maximilians-Universität München, Munich, Germany
| | - Giatgen A Spinas
- Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zürich, University of Zürich, Zürich, Switzerland
| | - Claudia Cavelti-Weder
- Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zürich, University of Zürich, Zürich, Switzerland
| | - Philipp A Gerber
- Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zürich, University of Zürich, Zürich, Switzerland
| | - Michael Huber
- Institute of Medical Virology, University of Zürich, Zürich, Switzerland
| | - Alexandra Trkola
- Institute of Medical Virology, University of Zürich, Zürich, Switzerland
| | - Milo A Puhan
- Epidemiology, Biostatistics and Prevention Institute, University of Zürich, Zürich, Switzerland
| | - Wendy Wei-Lynn Wong
- and Department of Molecular Life Science, University of Zürich, Zürich, Switzerland
| | - Andreas Linkermann
- Department of Internal Medicine III, Technische Universität Dresden, Dresden 01307, Germany; Division of Nephrology, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA
| | - Viswanathan Mohan
- Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialties Centre, Chennai, Tamil Nadu, India
| | - Hendrik Lehnert
- Presidential Office, Paris Lodron Universität Salzburg, Salzburg, Austria
| | - Peter Nawroth
- Department of Internal Medicine III, Technische Universität Dresden, Dresden 01307, Germany
| | - Triantafyllos Chavakis
- Paul Langerhans Institute Dresden, Helmholtz Munich, Technische Universität Dresden, Dresden 01307, Germany; Institute for Institute of Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden, Dresden 01307, Germany; German Center for Diabetes Research, Neuherberg, Germany; Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
| | - Geltrude Mingrone
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy; Division of Diabetes and Nutritional Sciences, School of Cardiovascular and Metabolic Medicine and Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Christian Wolfrum
- Laboratory of Translational Nutrition Biology, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zürich, Schwerzenbach, Switzerland
| | - Annelies S Zinkernagel
- Department of Infectious Diseases and Hospital Epidemiology, University of Zürich, Zürich, Switzerland
| | - Stefan R Bornstein
- Department of Internal Medicine III, Technische Universität Dresden, Dresden 01307, Germany; Paul Langerhans Institute Dresden, Helmholtz Munich, Technische Universität Dresden, Dresden 01307, Germany; German Center for Diabetes Research, Neuherberg, Germany; Division of Diabetes and Nutritional Sciences, School of Cardiovascular and Metabolic Medicine and Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
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Wong R, Lam E, Bramante CT, Johnson SG, Reusch J, Wilkins KJ, Yeh HC. Does COVID-19 Infection Increase the Risk of Diabetes? Current Evidence. Curr Diab Rep 2023; 23:207-216. [PMID: 37284921 PMCID: PMC10244847 DOI: 10.1007/s11892-023-01515-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/18/2023] [Indexed: 06/08/2023]
Abstract
PURPOSE OF REVIEW Multiple studies report an increased incidence of diabetes following SARS-CoV-2 infection. Given the potential increased global burden of diabetes, understanding the effect of SARS-CoV-2 in the epidemiology of diabetes is important. Our aim was to review the evidence pertaining to the risk of incident diabetes after COVID-19 infection. RECENT FINDINGS Incident diabetes risk increased by approximately 60% compared to patients without SARS-CoV-2 infection. Risk also increased compared to non-COVID-19 respiratory infections, suggesting SARS-CoV-2-mediated mechanisms rather than general morbidity after respiratory illness. Evidence is mixed regarding the association between SARS-CoV-2 infection and T1D. SARS-CoV-2 infection is associated with an elevated risk of T2D, but it is unclear whether the incident diabetes is persistent over time or differs in severity over time. SARS-CoV-2 infection is associated with an increased risk of incident diabetes. Future studies should evaluate vaccination, viral variant, and patient- and treatment-related factors that influence risk.
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Affiliation(s)
- Rachel Wong
- Department of Biomedical Informatics, Stony Brook University, Stony Brook, NY USA
- Health Science Center, Stony Brook Medical Center, Level 3, Room 45101 Nicolls Road, Stony Brook, NY 11794 USA
| | - Emily Lam
- Department of Biomedical Informatics, Stony Brook University, Stony Brook, NY USA
| | - Carolyn T. Bramante
- Division of General Internal Medicine, University of Minnesota Medical School, Minneapolis, MN USA
| | - Steven G. Johnson
- Institute for Health Informatics, University of Minnesota, Minneapolis, MN USA
| | - Jane Reusch
- Division of Endocrinology, Metabolism & Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO 80045 USA
| | - Kenneth J. Wilkins
- Biostatistics Program/Office of Clinical Research Support, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD USA
| | - Hsin-Chieh Yeh
- Department of Medicine, Johns Hopkins University, Baltimore, MD USA
- Department of Epidemiology, Johns Hopkins University, Baltimore, MD USA
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Lexner J, Lindroth Y, Sjöberg K. The risk for celiac disease after Covid-19 infection. BMC Gastroenterol 2023; 23:174. [PMID: 37217874 DOI: 10.1186/s12876-023-02795-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Accepted: 04/30/2023] [Indexed: 05/24/2023] Open
Abstract
BACKGROUND Celiac disease (CD) is an autoimmune disease leading to gastrointestinal symptoms and mineral deficiencies. The pathogenetic mechanisms, besides the clear HLA association, are elusive. Among environmental factors infections have been proposed. Covid-19 infection results in a systemic inflammatory response that often also involves the gastrointestinal tract. The aim of the present study was to investigate whether Covid-19 infection could increase the risk for CD. PATIENTS AND METHODS All patients, both children and adults, in the county Skåne (1.4 million citizens) in southern Sweden with newly diagnosed biopsy- or serology-verified CD or a positive tissue transglutaminase antibody test (tTG-ab) during 2016-2021 were identified from registries at the Departments of Pathology and Immunology, respectively. Patients with a positive Covid-19 PCR or antigen test in 2020 and 2021 were identified from the Public Health Agency of Sweden. RESULTS During the Covid-19 pandemic (March 2020 - December 2021), there were 201 050 cases of Covid-19 and 568 patients with biopsy- or serology-verified CD or a first-time positive tTG-ab tests, of which 35 patients had been infected with Covid-19 before CD. The incidence of verified CD and tTG-ab positivity was lower in comparison to before the pandemic (May 2018 - February 2020; 22.5 vs. 25.5 cases per 100 000 person-years, respectively, incidence rate difference (IRD) -3.0, 95% CI -5.7 - -0.3, p = 0.028). The incidence of verified CD and tTG-ab positivity in patients with and without prior Covid-19 infection was 21.1 and 22.4 cases per 100 000 person-years, respectively (IRD - 1.3, 95% CI -8.5-5.9, p = 0.75). CONCLUSIONS Our results indicate that Covid-19 is not a risk factor for CD development. While gastrointestinal infections seem to be an important part of the CD pathogenesis, respiratory infections probably are of less relevance.
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Affiliation(s)
- Jesper Lexner
- Department of Gastroenterology and Nutrition, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden
| | - Ylva Lindroth
- Division of Medical Microbiology, Department of Laboratory Medicine, Skåne University Hospital, Lund University, Lund, Sweden
| | - Klas Sjöberg
- Department of Gastroenterology and Nutrition, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden.
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Zucchini S, Scozzarella A, Maltoni G. Multiple influences of the COVID-19 pandemic on children with diabetes: Changes in epidemiology, metabolic control and medical care. World J Diabetes 2023; 14:198-208. [PMID: 37035223 PMCID: PMC10075036 DOI: 10.4239/wjd.v14.i3.198] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 01/28/2023] [Accepted: 02/23/2023] [Indexed: 03/15/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has heavily affected health worldwide, with the various forms of diabetes in children experiencing changes at various levels, including epidemiology, diabetic ketoacidosis rates and medical care. Type 1 diabetes showed an apparent increase in incidence, possibly owing to a direct damage of the virus to the β-cell. Diabetic ketoacidosis also increased in association with the general fear of referring patients to the hospital. Most children with diabetes (both type 1 and type 2) did not show a worsening in metabolic control during the first lockdown, possibly owing to a more controlled diet by their parents. Glucose sensor and hybrid closed loop pump technology proved to be effective in all patients with type 1 diabetes during the pandemic, especially because the downloading of data allowed for the practice of tele-medicine. Telemedicine has in fact grown around the world and National Health Systems have started to consider it as a routine activity in clinical practice. The present review encompasses all the aspects related to the effects of the pandemic on the different forms of diabetes in children.
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Affiliation(s)
- Stefano Zucchini
- Department of Pediatric, IRCCS AOU di Bologna, Bologna 40138, Italy
| | | | - Giulio Maltoni
- Department of Pediatric, IRCCS AOU di Bologna, Bologna 40138, Italy
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